Transgenic animals bearing human Igλ light chain genes

Abstract

The invention relates to transgenic animals bearing one or more human λ light chain loci. The invention also relates to methods and compositions for making transgenic animals that have incorporated human λ light chain loci. The invention further relates to methods of using and compositions derived from the transgenic animals that have incorporated human λ light chain loci.

1. A transgenic mouse whose genome comprises a substantially complete human λ light chain locus comprising V, J, and constant region genes, wherein the mouse comprises YAC yL. 
     
     
       2. The transgenic mouse according to  claim 1 , wherein said mouse further comprises a human immunoglobulin heavy chain locus comprising V, D, J, and constant region genes or a portion thereof, a human immunoglobulin κ light chain locus comprising V, J, and constant region genes or a portion thereof or both said human immunoglobulin heavy chain locus or portion thereof and said human immunoglobulin κ light chain locus or portion thereof. 
     
     
       3. A transgenic mouse whose genome comprises:
 a) a substantially inactivated endogenous heavy chain locus; 
 b) a substantially inactivated endogenous κ light chain locus; 
 c) a human heavy chain locus comprising V, D, J, and constant region genes; 
 d) a human κ light chain locus comprising V, J, and constant region genes; and 
 e) a substantially complete human λ light chain locus comprising V, J, and constant region genes, 
 
       wherein the mouse comprises YAC yL. 
     
     
       4. A method for producing a cell line that produces a human monoclonal antibody or a fragment thereof directed to an antigen, comprising:
 a) immunizing the transgenic mouse of  claim 2  or  3  with said antigen; 
 b) allowing said transgenic mouse to mount an immune response to said antigen; 
 c) isolating B lymphocytes from said transgenic mouse; 
 d) immortalizing said B lymphocytes; 
 e) creating individual monoclonal populations of said immortalized B-lymphocytes; and 
 f) screening said immortalized B lymphocytes to identify a cell line that produces an antibody directed to said antigen. 
 
     
     
       5. A cell line produced by the method according to  claim 4 . 
     
     
       6. The transgenic mouse of  claim 1 , comprising an active endogenous lambda light chain locus. 
     
     
       7. The transgenic mouse of  claim 2 , wherein the human immunoglobulin heavy chain locus is introduced by a YAC. 
     
     
       8. The transgenic mouse of  claim 3 , wherein the transgenic mouse expresses human Ig-kappa chains and human Ig-lambda chains in a ratio of 60:40. 
     
     
       9. A method for producing a B lymphocyte that produces a human monoclonal antibody or a fragment thereof directed to an antigen, comprising:
 a) immunizing the transgenic mouse of  claim 2  or  3  with said antigen; 
 b) allowing said transgenic mouse to mount an immune response to said antigen; 
 c) isolating B lymphocytes from said transgenic mouse; and 
 d) screening said B lymphocytes to identify a cell that produces an antibody directed to said antigen.